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Melanie Cole (Host): As the number of pediatric cancer survivors continues to grow, as treatments become more effective, considerations regarding the long-term effects of therapy on future fertility have become more important. My guest today is Dr. Holly Hoefgen. She an Assistant Professor in Pediatric and Adolescent Gynecology and the Co-Director of the Integrated Care and Fertility Preservation Program at St. Louis Children’s Hospital. Dr. Hoefgen, what are some of the possible complications that can arise in a pediatric cancer patient in terms of fertility?

Holly Hoefgen, MD (Guest): So, when our patients are going through their cancer treatments, we are in a rush to make sure we can work towards their survival, but now that they are getting better as you mentioned, our concerns are that we can also have these effects on their gonads and so this can lead to them having not only a loss of fertility but also a subfertility and so we want to be talking to the patients in advance of their treatments if at all possible to make sure that they are aware of these risks and if we can, to be able to talk to them about options to be able to preserve fertility in some of these patients.

Melanie: Speak about the field of pediatric fertility preservation a little bit Dr. Hoefgen and what makes you based on your expertise, best suited for this specialty?

Dr. Hoefgen: Yeah, so the field of fertility preservation in general, is somewhat new so, as we have started to notice that there has been a loss of fertility in patients; we wanted to make a change in that and there are studies that show that patients are definitely interested in talking about this loss of fertility. We see that about 75% of cancer survivors without children are interested in having children in the future. And we know that this is important in both male and female survivors and not only whether or not they want to have children, but just having the knowledge of the risks of their treatments and the risks of infertility is important to them. So, both the governing bodies of physicians from the oncology world and the reproductive world have all put forth statements to say that we should be talking to patients about these risks and making options available to them. So, as a gynecologist, pediatric gynecologist by training, I obviously have more of a focus on our female patients, but I have worked closely in my previous institution as the lead of the previous fertility preservation program where we worked with both the male and female patients and we would see all of the patients, talk to them about the risks of infertility and then guide them through the different options and I lead that program which was kind of a leader in the field and now moving back to the St. Louis area, wanting to bring that same sort of a program here to St. Louis Children’s Hospital.

Melanie: So, you said as early as possible in their treatment or even pretreatment that you are discussing this preservation and it should be considered. Speak about the quality of evidence supporting current and forthcoming options for preservation. Speak a little bit about what you say to the families and to the children themselves if they are in prepubescence or even if they are going through puberty. How do you discuss this with them?

Dr. Hoefgen: Yeah, so basically, we come to the family then we are bringing to them the idea that even though we are very focused on your treatment now, our goal is always to get your daughter or your son through their treatment, right so we also want to talk about how their quality of life is going to be after their treatment. And I discuss with them that we do have studies showing that this is important to survivors and so we want to make sure that we are talking about that. And the risks are different depending on the treatment that patients are going through. Some treatments are very low-risk for a future infertility. But other treatments such as bone marrow transplant or patients with high-dose radiation or certain types of chemotherapy can be very high-risk. And so especially in those patients, we want to make sure that they are aware of the fact that the treatment is high-risk and the fact that there may be options available to them. And we talk to patients as young as one-month old infants and up to adults to be able to discuss the fact that these things are available.

Melanie: So, let’s speak about some of the options that are available to preserve fertility before treatment begins and do these affect how well the cancer treatment works, whatever you are doing, the pre-treatment whether it is menstrual suppression or contraception. Do any of these things affect cancer treatment and then go into post treatment and how do you know if it is working?

Dr. Hoefgen: Yeah, so the options that we are talking to the patient about do not have an affect on their actual chemotherapy treatment. There has been concern before that we want to get the patient started on their chemotherapy and there is always a time limitation right, because we want to make sure that we are not delaying their therapy which would be the one thing that there could be a hold on because obviously, if we are trying to be able to preserve the patient’s fertility sometimes, this does take a little bit of time and that would be the one thing where we might cause an impact. So, we do have a discussion with the patient’s primary team to say what are – how is this patient – what is their state, are we able to take the time to be able to offer them these treatments?

But when we look at patients, and so for a female patient, in a prepubertal patient, we can offer them ovarian tissue cryopreservation which is being able to take the patient’s ovary in a surgical manner and be able to freeze part of that ovary for the patient to then be able to go through their treatments and then at a later date, be able to use that. Currently, that tissue is being re-implanted back into the body either on the ovary that’s left behind or in the area where the previous ovary was. But science is slowly to the fact that hopefully at some point we would also be able to just stimulate that ovary in a lab and be able to utilize some of those cells. That is currently experimental, so there are some caveats to being able to provide that.

In our patients that are a little older, we are able to preserve their eggs and their embryos and then that can take a little bit of time and require some stimulation of the patient’s ovaries. So, that in patients who may have estrogen or progesterone stimulatable cancers, we would not consider that. But that usually doesn’t fall into our pediatric and adolescent in population. And then for out male patients, for our older patients, we are able to bank sperm for those patients who are able to provide a sample and then in our prepubertal patients, is similar to how we are doing with the ovaries, we are able to take a sample of their testicular tissue and freeze that with the hopes that they can use that in the future to provide a future fertility.

Melanie: Dr. Hoefgen, when should a pediatrician refer to a specialist and explain a little bit about the role of the oncologist in advising patients about fertility preservation options.

Dr. Hoefgen: Yeah so, what we are trying to create now is a program where the referral base is actually coming through patients which are new to the oncology center here at St. Louis Children’s Hospital. So, our goal would be to talk to all patients who come through the pediatric hematology and oncology department so that every patient that receives a new diagnosis is consulted to the integrated care fertility preservation program. I think that’s important because even the patients who are low-risk for infertility deserve the education of knowing that. It’s important for patients to know that the chemotherapy I’m receiving does have a risk or the treatment that I’m receiving does have a risk to my fertility, but that risk is low. Up to the patients who are high-risk, and we are discussing some of these preservation options. And it’s also helpful because the families discuss their treatments and they discuss what’s happening when they are on the floor or when they are going through their treatments or in this age of social media, right everyone is discussing and understanding what’s going on and the people around them and so if they see well my neighbor was offered this treatment and I wasn’t, and why is that; well then they all understand why because they have each had a consult and they have each understood that. So, our goal is to make it so it becomes more automatic that every patient would receive that when they receive their initial diagnosis.

Melanie: If a child has already been through cancer treatment, is it too late to consider fertility preservation and after treatment, how do you know if the child’s fertility has been affected?

Dr. Hoefgen: Right, that’s a great question. And absolutely not. We want to make sure that there is an understanding that fertility preservation and this idea of the risk is something that we should talk about. Ideally, we want to talk about it in the beginning, but it’s a conversation that should continue throughout the spectrum of a patient’s treatment. So, we want to be available to the patients before, during and after their treatment. And especially for our female patients, commonly I would like to see all of those patients at about a year after their treatment so that we can kind of regenerate this discussion again and I like to see them again, go over the risks that we talked about in the beginning. We will usually do a little bit of laboratory panel, so we can see what actually did happen to their fertility from their chemotherapy. So, when we talked about the risks to their fertility, before their treatment, we are saying this is the risk of what could happen. After the fact, we are kind of trying to find out okay, based on that risk, what do we see now? What actually – where are we with your fertility at this standpoint? And then we do have options for those patients who either were not able to or who chose not to do fertility preservation options before their treatment, if they do still have fertility and are considered high-risk for possibly continuing to lose some of that fertility function; that we can offer options to patients either in the post-treatment phase or an inter-treatment phase to allow them to make that choice at a separate time.

Melanie: Other than fertility, what other gynecologic concerns would you recommend discussing with pediatric and adolescent oncology patients and what else would you like a referring physician to know about oncofertility preservation at St. Louis Children’s Hospital?

Dr. Hoefgen: Yeah, so there’s a huge other part of what we do and what this program is going to be and that is our gynecologic portion. So, just like any other adolescent teenager, right, these patients are still in need of a discussion of their menstrual cycle needs and their contraception needs and especially when patients are about to undergo chemotherapy. This is definitely the time that we want to make sure that we don’t have an unwanted teen pregnancy. So, in all of our pretreatment patients, we have a discussion about contraception and sexual health and making sure that we have a reliable form of contraception on board for patients for which that is necessary. And also, in many patients depending on their diagnosis, there may be a concern that in patients who are going to have a very low blood count based on either their underlying primary diagnosis or on the treatment that they are going to receive that having heavy menstrual cycles or having periods in general may be more than their body is able to handle at that point. And so, we talk about ways to help control their menstrual cycles during their treatment. So, those are things that we talk to patients before and during their treatment.

The survivorship time is actually a very important time for patients to see a gynecologist. Because there is a lot of these sort of secondary affects of medication that can affect the gynecologic standpoint. So, same as what we just discussed, we still talk about periods and we still talk about contraception but the same way that these medicines can affect the ovaries as far as fertility, they can affect the ovaries as far as the patient’s hormones as well. So, if a patient’s ovary isn’t functioning, they can also lose the hormones which means that they may be in what commonly would be referred to as an early menopause, so we will label that as a primary ovarian insufficiency and this is even more important to make sure that we are taking care of in our adolescent patients because they are growing their bones, they may not have fully developed prior to their chemotherapy and we want to make sure that we are getting them through all of those milestones and there can be also worries as far as genital graph versus host disease and some other HPV related diseases that can be very important in these patients.

So, there is a wide range of things that we need to see patients for and meet patients for in that realm and as far as your questions for a general pediatrician, I think in the survivor standpoint is really where a lot of this can fall back to the general pediatrician because once they start – they are kind of no longer seeing their oncologist and maybe going back to their primary visits is when a lot of these late affects scenarios start to come up and may not even be noticed that that is a late affect of their chemotherapy. But if these things are coming, then we very much would like to see them back for those type of issues.

Melanie: Thank you so much for being on with us today. What a fascinating topic Dr. Hoefgen and thank you so much for being with us. A physician can refer a patient by calling the Children’s Direct Physician Access Line at 1-800-678-HELP, that’s 1-800-678-4357. You’re listening to Radio Rounds with St. Louis Children’s Hospital. For more information on resources available at St. Louis children’s Hospital, you can go to www.stlouischildrens.org, that’s www.stlouischildrens.org. This is Melanie Cole. Thanks so much for listening.